FGF was first identified as a mitogenic pituitary hormone in the 1970's (Gospedarowicz, D. 1974 Nature 249:123-127). Thereafter, factors present in primarily brain and pituitary tissues were shown capable of stimulating the growth of a number of different cell types, including endothelial cells, fibroblast cells, retinal cells, and others. Only recently, with the cloning of genes encoding the various growth factors, has it become clear that most of the activities reside in two microheterogeneous proteins, basic and acidic FGF's (see, Gospedarowicz, D., (1986) Mol. and Cell. Endocrin. 46:187-204, which is incorporated herein by reference).
Basic and acidic FGF's have now been isolated from many diverse sources and by a variety of purification schemes. Although the production of cDNA and genomic clones encoding FGF precursors have demonstrated the common identity of the various growth factors, new issues have been raised concerning their biology. For example, the cDNA clones of the FGF's did not include classical signal sequences generally associated with secreted proteins. Also, various research groups have reported different NH2-terminus amino acids, as well as varying lengths of the overall FGF proteins.
In order to accurately decipher the different biological characteristics, if any, of the microheterogeneous forms of FGF, it is necessary to establish recombinant expression systems for the production of the various FGF forms. The expression systems should be capable of post-translational modification in the native fashion, including amino-terminal acetylation. Ideally, the systems will also provide for high expression levels of the proteins in forms that can be readily purified, all in an economical manner. The present invention fulfills these and other needs.